TOPLINE:

In a meta-analysis, lurasidone outperformed placebo in alleviating depressive symptoms across multiple psychiatric diagnoses including schizophrenia, bipolar disorder, and major depressive disorder (MDD), with better acceptability and safety and comparable tolerability.

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of randomised controlled trials comparing the effect of lurasidone with that of placebo on depressive symptoms across psychiatric diagnoses.
• They included 14 randomised, double-masked, placebo-controlled trials comprising 5239 participants with diagnoses of schizophrenia experiencing acute psychotic exacerbation, bipolar I disorder, or MDD with mixed features.
• Participants received daily doses of lurasidone ranging from 20 to 120 mg, either as fixed doses or flexibly dosed regimens, with most trials lasting 6 weeks except for one 28-week-long open-label study.
• The primary outcome was the mean change in the severity of depressive symptoms, measured using the Montgomery-Åsberg Depression Rating Scale or other validated scales; secondary outcomes were acceptability, tolerability, and safety.
• The risk of bias was assessed using the Cochrane Risk of Bias Tool 2.

TAKEAWAY:

• In the pooled analysis, lurasidone was superior to placebo in improving depression scores (standardised mean difference [SMD], -0.26; 95% CI, -0.37 to -0.15) across multiple diagnoses. The largest effect size was observed in patients with MDD with mixed features (Hedge's g, -0.73; 95% CI, -1.01 to -0.45).
• Lurasidone use was associated with better treatment acceptability (relative risk [RR], 0.55; 95% CI, 0.43-0.71) and safety (RR, 0.73; 95% CI, 0.58-0.91) than placebo use, with comparable tolerability (RR, 0.74; 95% CI, 0.54-1.02).
• A subgroup analysis in patients with bipolar disorder aligned with the primary analysis (SMD, -0.27; 95% CI, -0.39 to -0.14); however, the analysis in those with schizophrenia showed weaker evidence of benefit (SMD, -0.19; 95% CI, -0.35 to -0.03).
• Five out of 14 trials had a high risk of bias, whereas others had a low risk of bias.

IN PRACTICE:

"Our findings suggest that lurasidone is a useful psychopharmacological tool for treating depressive symptoms in a variety of patients with severe mental illness," the authors wrote. "To support updates to clinical guidelines, further large-scale trials with robust designs, longer follow-up and pragmatic dosing regimens are needed. Future research examining depressive symptoms transdiagnostically may also identify patient subgroups who would most benefit from lurasidone," they added.

SOURCE:

This study was led by Ana Ghenciulescu, BM, BCh, and Anna Pearse, BM, BCh, Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford, England. It was published online on August 20 in The British Journal of Psychiatry.

LIMITATIONS:

This study was limited by a high risk of bias in multiple included studies, improper handling of missing data, and substantial heterogeneity in dosing, settings, design, and the findings. Most included trials had relatively short follow-up periods of 6 weeks, limiting the understanding of long-term efficacy and lowering the certainty of evidence. Additionally, all trials included disclosed sponsorship by a pharmaceutical company manufacturing lurasidone, with several being authored by its employees.

DISCLOSURES:

This study did not receive any specific grant from any funding agency. One author reported being a part of the editorial board for The British Journal of Psychiatry.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.